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1.
Tech Coloproctol ; 27(11): 1047-1056, 2023 11.
Article in English | MEDLINE | ID: mdl-36906661

ABSTRACT

PURPOSE: Adequate staging of early rectal neoplasms is essential for organ-preserving treatments, but magnetic resonance imaging (MRI) frequently overestimates the stage of those lesions. We aimed to compare the ability of magnifying chromoendoscopy and MRI to select patients with early rectal neoplasms for local excision. METHODS: This retrospective study in a tertiary Western cancer center included consecutive patients evaluated by magnifying chromoendoscopy and MRI who underwent en bloc resection of nonpedunculated sessile polyps larger than 20 mm, laterally spreading tumors (LSTs) [Formula: see text] 20 mm, or depressed-type lesions of any size (Paris 0-IIc). Sensitivity, specificity, accuracy, and positive and negative predictive values of magnifying chromoendoscopy and MRI to determine which lesions were amenable to local excision (i.e., [Formula: see text] T1sm1) were calculated. RESULTS: Specificity of magnifying chromoendoscopy was 97.3% (95% CI 92.2-99.4), and accuracy was 92.7% (95% CI 86.7-96.6) for predicting invasion deeper than T1sm1 (not amenable to local excision). MRI had lower specificity (60.5%, 95% CI 43.4-76.0) and lower accuracy (58.3%, 95% CI 43.2-72.4). Magnifying chromoendoscopy incorrectly predicted invasion depth in 10.7% of the cases in which the MRI was correct, while magnifying chromoendoscopy provided a correct diagnosis in 90% of the cases in which the MRI was incorrect (p = 0.001). Overstaging occurred in 33.3% of the cases in which magnifying chromoendoscopy was incorrect and 75% of the cases in which MRI was incorrect. CONCLUSION: Magnifying chromoendoscopy is reliable for predicting invasion depth in early rectal neoplasms and selecting patients for local excision.


Subject(s)
Colonoscopy , Rectal Neoplasms , Humans , Colonoscopy/methods , Retrospective Studies , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/surgery , Predictive Value of Tests , Neoplasm Staging
2.
Braz J Med Biol Res ; 55: e12141, 2022.
Article in English | MEDLINE | ID: mdl-36350971

ABSTRACT

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.


Subject(s)
Alphapapillomavirus , Anus Neoplasms , Atypical Squamous Cells of the Cervix , Crohn Disease , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Crohn Disease/complications , Anus Neoplasms/pathology , Immunosuppressive Agents/therapeutic use
3.
Braz. j. med. biol. res ; 55: e12141, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403910

ABSTRACT

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

4.
Rev Gastroenterol Mex (Engl Ed) ; 85(2): 180-189, 2020.
Article in English, Spanish | MEDLINE | ID: mdl-32057523

ABSTRACT

INTRODUCTION AND AIM: Surgery for distal rectal cancer (DRC) can be performed with or without sphincter preservation. The aim of the present study was to analyze the outcomes of two surgical techniques in the treatment of DRC patients: low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: Patients with advanced DRC that underwent surgical treatment between 2002 and 2012 were evaluated. We compared the outcomes of the type of surgery (APR vs LAR) and analyzed the associations of survival and recurrence with the following factors: age, sex, tumor location, lymph nodes obtained, lymph node involvement, and rectal wall involvement. Patients with distant metastases were excluded. RESULTS: A total of 148 patients were included, 78 of whom were females (52.7%). The mean patient age was 61.2years. Neoadjuvant chemoradiation therapy was performed in 86.5% of the patients. APR was performed on 86 (58.1%) patients, and LAR on 62 (41.9%) patients. No differences were observed between the two groups regarding clinical and oncologic characteristics. Eighty-seven (62%) patients had pT3-4 disease, and 41 patients (27.7%) had lymph node involvement. In the multivariate analysis, only poorly differentiated tumors (P=.026) and APR (P=.009) correlated with higher recurrence rates. Mean follow-up time was 32 (16-59.9) months. Overall 5-year survival was 58.1%. The 5-year survival rate was worse in patients that underwent APR (46.5%) than in the patients that underwent LAR (74.2%) (P=.009). CONCLUSIONS: Patients with locally advanced DRC that underwent APR presented with a lower survival rate and a higher local recurrence rate than patients that underwent LAR. In addition, advanced T/stage, lymph node involvement, and poor tumor differentiation were associated with recurrence and a lower survival rate, regardless of the procedure.


Subject(s)
Colon, Sigmoid/surgery , Proctectomy , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hospitals, University , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Survival Analysis , Treatment Outcome
6.
Endosc Int Open ; 6(5): E531-E540, 2018 May.
Article in English | MEDLINE | ID: mdl-29713679

ABSTRACT

BACKGROUND AND STUDY AIMS: To determine the clinical features associated with advanced duodenal and ampullary adenomas in familial adenomatous polyposis. Secondarily, we describe the prevalence and clinical significance of jejunal polyposis. PATIENTS AND METHODS: This is a single center, prospective study of 62 patients with familial adenomatous polyposis. Duodenal polyposis was classified according to Spigelman and ampullary adenomas were identified. Patients with Spigelman III and IV duodenal polyposis underwent balloon assisted enteroscopy. Predefined groups according to Spigelman and presence or not of ampullary adenomas were related to the clinical variables: gender, age, family history of familial adenomatous polyposis, type of colorectal surgery, and type of colorectal polyposis. RESULTS: Advanced duodenal polyposis was present in 13 patients (21 %; 9 male) at a mean age of 37.61 ±â€Š13.9 years. There was a statistically significant association between family history of the disease and groups according to Spigelman ( P  = 0.03). Seven unrelated patients (6 male) presented ampullary adenomas at a mean age of 36.14 ±â€Š14.2 years. The association between ampullary adenomas and extraintestinal manifestations was statistically significant in multivariate analysis ( P  = 0.009). Five endoscopic types of non-ampullary adenoma were identified, showing that lesions larger than 10 mm or with a central depression presented foci of high grade dysplasia. Among 28 patients in 12 different families, a similar Spigelman score was identified; 10/12 patients (83.3 %) who underwent enteroscopy presented small tubular adenomas with low grade dysplasia in the proximal jejunum. CONCLUSIONS: Advanced duodenal polyposis phenotype may be predictable from disease severity in a first-degree relative. Ampullary adenomas were independently associated with the presence of extraintestinal manifestations.

7.
Tech Coloproctol ; 21(9): 755, 2017 09.
Article in English | MEDLINE | ID: mdl-28900885

ABSTRACT

Unfortunately, one of the author name was wrongly published in the original publication. The complete correct name should read as follows "Beatriz Camargo Azevedo". The original article was updated.

8.
J Adv Res ; 8(6): 617-625, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28819569

ABSTRACT

The genetic markers in inflammatory responses during mastitis afford a reasonable way for improving milk production in the Egyptian buffalo breed. Among them is the interleukin 8 Receptor Gene (IL8RB) (CXCR2); a chemokine receptor gene augments the neutrophil migration during infection. To understand its role better during mastitis in Egyptian buffalos, twenty-five dairy animals representing the normal, sub-clinically, clinically and chronically affected buffalos were randomly selected from different districts. Screening criteria for mastitis were based on somatic cell count and California mastitis test assays on their milk samples. Biochemically, mastitis induced an increase in milk lactate dehydrogenase, alkaline phosphatase and catalase activities and serum malanoaldehyde concentration. The total antioxidant concentrations, however, decreased in serum and milk during mammary inflammation. The protein profiling of milk whey proved an accelerated mammary inflammatory influx of blood-borne proteins during mastitis. The genomic DNAs were extracted from blood samples and the CXCR2 sequence of 1246 bp covering a part of intron 1, exon 2 and a part of 3'UTR were submitted to Genbank (accession # KY399457.1). The study clearly defined the presence of four SNPs. Three were detected as synonymous substitutions in coding region and one in the 3'UTR region. Only SNP C/A at c.127 was found to be highly associated with mastitis. In conclusion, the results warrant the potential correlation between the genetic SNP variance for certain genes and the incidence of mastitis in buffalo breed.

9.
Tech Coloproctol ; 21(9): 745-754, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28819868

ABSTRACT

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) for rectal cancer may lead to cure. As we currently lack reliable methods to clinically confirm the absence of disease, some patients undergo radical resection and have pathological complete response (pCR) still undergo surgery. Furthermore, it is uncertain if conventional one-level histopathological analysis is accurate enough to determine complete response. Confirming pCR is essential to determine the prognosis and to consider the patient's inclusion in trials of adjuvant therapy. The aim of this study was to determine whether the current 1-level approach is sufficient to confirm pCR. METHODS: Four hundred and thirty-five patients with rectal cancer who received nCRT followed by radical resection were analyzed. All cases identified as pCR by 1-level step section histological evaluation were reassessed with 3-level step sections and immunohistochemical analysis to verify the presence of residual disease. RESULTS: Out of 435 patients, 75 (17.2%) were staged as ypT0. Of these, 6 had lymph node involvement and 1 had distant metastasis, leaving 68 (15.6%) who had pCR. After the additional step sections, residual tumor was detected in 12 (17.6%) of these 68. The final pCR rate was 12.9%. Distant recurrence was detected in 7.1% of real-pCR patients compared to 16.7% in the false-pCR group (p = 0.291). Sensitivity of clinical assessment for detecting pCR was 35.7%, and the accuracy of 1-section histological evaluation to identify pCR was 82.4%. CONCLUSIONS: Histopathological analysis with 1-level step section is insufficient to determine complete tumor eradication. The 3-level sections methodology revealed residual tumor cells in patients initially classified as ypT0. Further studies with larger sample size are required to verify the clinical relevance of these residual tumor cells. Caution should continue to be applied to watch and wait strategies following nCRT.


Subject(s)
Chemoradiotherapy, Adjuvant/methods , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/diagnosis , Neoplasm, Residual/diagnosis , Rectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Colectomy/methods , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasm, Residual/pathology , Prognosis , Prospective Studies , Rectal Neoplasms/therapy , Rectum/pathology , Retrospective Studies , Treatment Outcome
10.
Int J Colorectal Dis ; 32(6): 925-927, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28035459

ABSTRACT

INTRODUCTION: Rectal cancer patients frequently present with locally advanced disease for which the standard of care includes neoadjuvant chemoradiotherapy followed by total mesorectal excision. Positive lymph nodes are one of the most powerful risk factors for recurrence and survival in colorectal cancer. In the absence of specific rectal guidelines, the literature recommends to the pathologist to optimize the number of rectal lymph nodes (LN) retrieved. We made a literature review in order to identify factors that could potentially affect the number of LN retrieved in specimens of patients with rectal cancer treated by chemoradiotherapy (CRT) followed by total mesorectal excision (TME). RESULTS: Age did not have a significant effect on LN yield. The effect of sex on LN number is not consistent in the literature. Most of the papers did not find a relationship between lower LN obtained and gender. Laparoscopy for primary rectal cancer is associated with a greater number of LN as well as short-term benefits. Tumors in the upper rectum are associated with a higher number of LN than those in the mid and lower rectum. The type of surgery had no effect on lymph node yield either. Tumors with complete or almost complete pathologic regression were exactly the ones with lower number of lymph nodes detected. Approximately one-third of patients with neoadjuvant treatment had less than 12 LN yield. CONCLUSION: The tumor regression grade is the most important factor for the decrease in the number of lymph nodes.


Subject(s)
Lymph Nodes/pathology , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Age Factors , Female , Humans , Lymph Nodes/surgery , Male , Rectal Neoplasms/surgery , Rectum/pathology , Rectum/surgery
11.
Rev Gastroenterol Mex ; 81(4): 202-207, 2016.
Article in English, Spanish | MEDLINE | ID: mdl-27717630

ABSTRACT

INTRODUCTION AND AIMS: Rectal prolapse is common in the elderly, having an incidence of 1% in patients over 65years of age. The aim of this study was to evaluate the safety and feasibility of a new endoluminal procedure for attaching the previously mobilized rectum to the anterior abdominal wall using an endoscopic fixation device. MATERIALS AND METHODS: The study is a single-arm phasei experimental trial. Under general anesthesia, total rectal prolapse was surgically reproduced in five pigs. Transanal endoscopic reduction of the rectal prolapse was performed. The best site for transillumination of the abdominal wall, suitable for rectopexy, was identified. The EndoLifter was used to approximate the anterior wall of the proximal rectum to the anterior abdominal wall. Two percutaneous rectopexies were performed by puncture with the Loop FixtureII Gastropexy Kit® at the preset site of transillumination. After the percutaneous rectopexies, rectoscopy and exploratory laparotomy were performed. Finally, the animals were euthanized. RESULTS: The mean procedure time was 16min (11-21) and the mean length of the mobilized specimen was 4.32cm (range 2.9-5.65cm). A total of 10 fixations were performed with a technical success rate of 100%. There was no evidence of postoperative rectal prolapse in any of the animals. The EndoLifter facilitated the process by allowing the mucosa to be held and manipulated during the repair. CONCLUSIONS: Endoscopic-assisted percutaneous rectopexy is a safe and feasible endoluminal procedure for fixation of the rectum to the anterior abdominal wall in experimental animals.


Subject(s)
Endoscopy, Gastrointestinal/instrumentation , Endoscopy, Gastrointestinal/methods , Rectal Prolapse/surgery , Animals , Feasibility Studies , Laparotomy , Sus scrofa , Swine
12.
Leukemia ; 30(3): 666-73, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26514544

ABSTRACT

Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53 VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS.


Subject(s)
Gene Frequency , Leukemia, Myeloid, Acute/diagnosis , Mutation , Myelodysplastic Syndromes/diagnosis , Phenotype , Tumor Suppressor Protein p53/genetics , Aged , Aged, 80 and over , Alleles , Core Binding Factor Alpha 2 Subunit/genetics , Cytogenetic Analysis , Female , Follow-Up Studies , Gene Expression , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Multivariate Analysis , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Nuclear Proteins/genetics , Phosphoproteins/genetics , Prognosis , RNA Splicing Factors , Ribonucleoprotein, U2 Small Nuclear/genetics , Ribonucleoproteins/genetics , Serine-Arginine Splicing Factors , Survival Analysis
13.
Br J Surg ; 102(5): 558-62, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25692968

ABSTRACT

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.


Subject(s)
Anal Canal/transplantation , Rectum/transplantation , Anal Canal/physiology , Analysis of Variance , Animals , Male , Manometry , Models, Animal , Operative Time , Pressure , Random Allocation , Rats, Wistar , Rectum/physiology , Transplantation, Autologous
15.
Tech Coloproctol ; 18(8): 699-708, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24509716

ABSTRACT

BACKGROUND: Molecular imaging using positron emission tomography/computerized tomography (PET/CT) may add relevant incremental diagnostic information to standard structural cross-sectional imaging. Such information may allow identification of patients with rectal cancer that are more likely to develop complete tumor regression after neoadjuvant chemoradiation therapy (CRT). The objective of this report was to identify PET/CT features that are associated with a complete response after CRT. METHODS: 99 cT2-4N0-2M0 distal rectal cancer patients (≤7 cm from anal verge) were included in this prospective single center trial (NCT 00254683). Patients underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based neoadjuvant CRT. After completion of therapy, patients underwent 6- and 12-week PET/CT. Clinical assessment of tumor response was performed at 12 weeks and was blinded to radiological information. Patients were treated according to clinical assessment. RESULTS: There were seven patients with a complete pathological response (pCR) and 16 with a complete clinical response (cCR) (23 complete responders). Comparison of pCR exclusively and non-pCR revealed that only baseline primary tumor standard uptake value (SUV) was a significant predictor of response. Comparison of complete responders (pCR or cCR) and non-complete responders showed that depth of rectal wall uptake at baseline PET/CT (p = 0.002) and variation between baseline and 12-week maximum standard uptake value (SUVmax) of primary tumor (p = 0.001) were independent predictors for complete response at multivariate analysis. A decrease >67 % between baseline and 6-week or 76 % between baseline and 12-week SUVmax were associated with complete response (pCR or cCR; p = 0.02 and p < 0.001, respectively). CONCLUSIONS: Positron emission tomography/computerized tomography at baseline, 6 and 12 weeks, may provide information regarding patients with a higher likelihood of developing complete tumor regression following neoadjuvant CRT.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/therapeutic use , Diagnostic Imaging , Positron-Emission Tomography/methods , Rectal Neoplasms/therapy , Adenocarcinoma/diagnosis , Chemoradiotherapy, Adjuvant , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Predictive Value of Tests , Prospective Studies , Rectal Neoplasms/diagnosis , Reproducibility of Results , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
16.
Curr Med Res Opin ; 29(7): 861-7, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23514092

ABSTRACT

Many efficacy endpoints have been used in clinical trials of acute migraine pharmacotherapy. Headache response or headache relief (i.e., moderate/severe pain reduced to mild/no pain) at a single, specified time-point, traditionally the primary endpoint, and headache recurrence (i.e., return of pain after initial postdose relief) are inadequate. Headache relief does not provide information about pain-free response and counts a partial response as a treatment success. Headache recurrence can reflect sustained efficacy but is confounded by initial response to treatment, because ineffective drugs have low recurrence rates. The International Headache Society (IHS) guidelines state that 2 hour pain-free response and sustained pain-free response (i.e., freedom from pain with no recurrence or use of rescue or study medication 2-24 hours postdose) provide the most clinically relevant information about the efficacy of migraine pharmacotherapy. The pain-free criterion counts partial responses as failures and thus is a more rigorous test of therapeutic benefit than headache relief, and the two endpoints together incorporate the main treatment attributes that determine patient satisfaction. As an example, consider needle-free subcutaneous sumatriptan and oral triptan tablets. An open-label study of needle-free subcutaneous sumatriptan by Cady and colleagues found that 2 hour pain-free response and sustained pain-free response were 64% and 42% respectively. For oral triptan tablets, the 2001 metaanalysis by Ferrari and colleagues reported 2 hour pain-free response rates ranging from 23% to 38% and sustained pain-free response rates ranging from 11% to 26%. The measures of pain-free response 2 hours postdose and sustained pain-free response can differentiate among treatments and be used to guide therapeutic choices.


Subject(s)
Migraine Disorders/drug therapy , Pain Management , Pain Measurement , Serotonin 5-HT1 Receptor Agonists/therapeutic use , Sumatriptan/therapeutic use , Humans , Pain/drug therapy , Patient Satisfaction , Research Design , Sumatriptan/analogs & derivatives , Treatment Outcome
17.
Colorectal Dis ; 15(6): 674-82, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23374979

ABSTRACT

AIM: Inguinal nodes may be a possible route for lymphatic spread in patients with distal rectal cancer. The outcome was examined for patients with distal rectal cancer undergoing neoadjuvant chemoradiation (CRT) and having 2-fluorine-18-fluoro-2-deoxy-d-glucose (FDG)-avid inguinal nodes using positron emission tomography/computed tomography (PET/CT) imaging. METHOD: Ninety-nine consecutive patients with cT2-4N0-2M0 distal rectal adenocarcinoma were enrolled in a clinical trial (NCT00254683) and underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based CRT. After CRT, patients underwent 6- and 12-week PET/CT. Patients with positive inguinal node uptake were compared with patients with negative uptake. The inguinal region was not included in the field of radiation therapy. RESULTS: Seventeen (17%) patients had baseline positive inguinal node FDG uptake. They were more likely to have the tumour closer to the anal verge (2.0 vs 4.2 cm; P = 0.001). Of these, eight (47%) demonstrated a positive inguinal uptake at PET/CT after 12 weeks from CRT. Patients with inguinal node FDG uptake after CRT (positive PET at baseline and 12 weeks) had a significantly worse 3-year overall and disease-free survival (P = 0.02 and P = 0.03). After a median follow-up period of 22 months, none of these patients had developed inguinal recurrence. CONCLUSION: Uptake of inguinal nodes at PET/CT may be present in up to 17% of patients with distal rectal cancer, particularly with ultra-low tumours. Nearly half of these nodes no longer show uptake after CRT despite the groin area not being included in the radiation field. Persistence of inguinal node uptake 12 weeks after CRT completion may be a marker for worse oncological outcome.


Subject(s)
Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/therapeutic use , Chemoradiotherapy, Adjuvant/methods , Fluorouracil/therapeutic use , Lymph Nodes/diagnostic imaging , Rectal Neoplasms/therapy , Adenocarcinoma/diagnostic imaging , Adult , Aged , Disease-Free Survival , Female , Fluorodeoxyglucose F18 , Humans , Inguinal Canal , Male , Middle Aged , Multimodal Imaging , Neoadjuvant Therapy/methods , Positron-Emission Tomography , Prognosis , Radiopharmaceuticals , Rectal Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome
18.
Cell Death Differ ; 18(9): 1500-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21394101

ABSTRACT

Maintaining genomic integrity is critical to avoid life-threatening disorders, such as premature aging, neurodegeneration and cancer. A multiprotein cascade operates at sites of DNA double-strand breaks (DSBs) to recognize, signal and repair damage. RNF168 (ring-finger nuclear factor) contributes to this emerging pathway of several E3 ubiquitin ligases that perform sequential ubiquitylations on damaged chromosomes, chromatin modifications essential for aggregation of repair complexes at the DSB sites. Here, we report the clinical and cellular phenotypes associated with a newly identified homozygous nonsense mutation in the RNF168 gene of a patient with a syndrome mimicking ataxia-telangiectasia. The mutation eliminated both of RNF168's ubiquitin-binding motifs, thus blocking progression of the ubiquitylation cascade and retention of repair proteins including tumor suppressors 53BP1 and BRCA1 at DSB sites, consistent with the observed defective DNA damage checkpoints/repair and pronounced radiosensitivity. Rapid screening for RNF168 pathway deficiency was achieved by scoring patients' lymphoblastoid cells for irradiation-induced nuclear foci containing 53BP1, a robust assay we propose for future diagnostic applications. The formation of radiation-induced DSB repair foci was rescued by ectopic expression of wild-type RNF168 in patient's cells, further causally linking the RNF168 mutation with the pathology. Clinically, this novel syndrome featured ataxia, telangiectasia, elevated alphafetoprotein, immunodeficiency, microcephaly and pulmonary failure and has implications for the differential diagnosis of autosomal recessive ataxias.


Subject(s)
Ataxia Telangiectasia/genetics , Codon, Nonsense , Ubiquitin-Protein Ligases/genetics , Adolescent , Ataxia Telangiectasia/diagnosis , Ataxia Telangiectasia/metabolism , Ataxia Telangiectasia/physiopathology , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , Diagnosis, Differential , Growth Disorders/genetics , Growth Disorders/physiopathology , Homozygote , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Male , Radiation Tolerance/genetics , Syndrome , Tumor Suppressor p53-Binding Protein 1 , Ubiquitin/genetics , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/deficiency
19.
Colorectal Dis ; 13(3): 317-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-19906053

ABSTRACT

AIM: Chagas' disease is an endemic parasitosis found in Latin America. The disease affects different organs, such as heart, oesophagus, colon and rectum. Megacolon is the most frequent long-term complication, caused by damage to the myoenteric and submucous plexus, ultimately leading to a functional barrier to the faeces. Patients with severe constipation are managed surgically. The study aimed to analyse the 10-year minimum functional outcome after rectosigmoidectomy with posterior end-to-side anastomosis (RPESA). METHOD: A total of 21 of 46 patients were available for follow up. Patients underwent clinical, radiological and manometric evaluation, and the results were compared with preoperative parameters. RESULTS: Of the 21 patients evaluated, 81% (17) were female, with a mean age of 60.6 years. Good function was achieved in all patients, with significant improvement in defaecatory frequency (P < 0.0001), usage of enemas (P < 0.0001) and patient satisfaction. Barium enema also showed resolution of the colonic and rectal dilatation in 19 cases evaluated postoperatively. CONCLUSION: Minimal 10-year follow up of RPESA showed excellent functional results, with no recurrence of constipation.


Subject(s)
Chagas Disease/complications , Colon, Sigmoid/surgery , Digestive System Surgical Procedures/methods , Megacolon/surgery , Rectum/surgery , Adult , Aged , Anal Canal/physiology , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Colon/anatomy & histology , Colon/diagnostic imaging , Constipation/surgery , Defecation , Female , Follow-Up Studies , Humans , Laxatives/therapeutic use , Male , Manometry , Megacolon/etiology , Megacolon/parasitology , Middle Aged , Radiography , Time Factors , Treatment Outcome , Young Adult
20.
Asian J Endosc Surg ; 4(3): 99-106, 2011 Aug.
Article in English | MEDLINE | ID: mdl-22776271

ABSTRACT

BACKGROUND: Laparoscopic colectomy is superior to open colectomy in terms of short-term surgical outcomes. There is solid evidence indicating that laparoscopic and open surgery are equally effective for colon cancer, but for rectal cancer, the issues of neoadjuvant treatment, the need for total mesorectal excision and autonomic nerve preservation, and the technical demands of a well-constructed low colorectal or coloanal anastomosis challenge even the most specialized surgeons. This review discusses the available evidence on short-term and long-term outcomes after laparoscopic total mesorectal excision for rectal cancer. DATA SOURCES: Systematic MEDLINE and Embase searches of outcomes on laparoscopic total mesorectal excision were conducted and data were retrieved. CONCLUSIONS: Information on short-term and long-term outcomes after laparoscopic total mesorectal excision remains limited. Data are mainly retrospective and from randomized studies based on few cases that had minimal follow-up. Early non-oncologic surgical outcomes seem improved after laparoscopy, but an increased rate of positive circumferential resection margins has been detected. Though scarce, the available evidence on recurrence and survival does not indicates disadvantages to the laparoscopic approach.


Subject(s)
Laparoscopy , Rectal Neoplasms/surgery , Rectum/surgery , Humans , Neoplasm Recurrence, Local , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Rectum/pathology , Treatment Outcome
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